An Outbreak of Severe Neonatal Pneumonia Caused by Human Respiratory Syncytial Virus BA9 in a Postpartum Care Centre in Shenyang, China

ABSTRACT Human respiratory syncytial virus (HRSV) is a major pathogen of lower respiratory tract infections in children (<5 years) and older individuals, with outbreaks mainly reported among infants in hospital pediatric departments and intensive care units (ICUs). An outbreak of severe neonatal pneumonia occurred in a postpartum center in Shenyang city, China, from January to February 2021. In total, 34 respiratory samples were collected from 21 neonates and 13 nursing staff. The samples were screened for 27 pathogens using a TaqMan low-density array, and 20 samples tested positive for HRSV, including 16 neonates and 4 nursing staff samples. Among the 16 hospitalized neonates, seven were admitted to an ICU and nine to general wards. Four of the nursing staff had asymptomatic infections. To investigate the genetic characteristics of the HRSV responsible for this outbreak, the second hypervariable region (HVR2) sequences of the G gene were obtained from six neonates and two nursing staff. Phylogenetic analyses revealed that all eight sequences (SY strains) were identical, belonging to the HRSV BA9 genotype. Our findings highlight the necessity for strict hygiene and disease control measures so as to prevent cross-infection and further avoid potential outbreaks of severe infectious respiratory diseases. IMPORTANCE Human respiratory syncytial virus (HRSV) is one of the leading causes of acute lower respiratory infections (ALRI) worldwide. In this study, we first reported an outbreak of severe neonatal pneumonia caused by HRSVB BA9 at a postpartum care center in mainland China. Among 20 confirmed cases, 16 were hospitalized neonates with 7 in the ICU ward, and the other four were nursing staff with asymptomatic infections. Our findings highlighted the importance of preventing cross-infection in such postpartum centers.

of ALRI such as cough, respiratory failure and even heart failure in neonates.

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Based on the molecular epidemiological investigation, environmental monitoring 73 of the postpartum care centre, and working patterns of the nursing staff, it is 74 speculated that the outbreak may have been caused by transmission of HRSV 75 asymptomatic nurses to neonates.

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Human respiratory syncytial virus (HRSV) is one of the most common 82 pathogens of acute lower respiratory infections (ALRI) in young children under 5 83 years of age, usually requiring hospitalization and mainly causing pneumonia and 84 bronchiolitis, and in even death severe cases (1, 2). The main manifestations of 85 ALRI caused by HRSV are a stuffy nose, runny nose and fever, cough, shortness of 86 breath, and respiratory failure(2). Its serious disease burden has aroused great 87 public concern. In 2015, an estimated 33.1 million children infected with HRSV-88 related ALRI were reported worldwide, of which 3.2 million children were 89 hospitalized(3) .

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HRSV is a negative-sense, single-stranded RNA virus of the genus 91 Orthopneumovirus, and the family Pneumoviridae (4). According to antigenic and 92 genetic differences, HRSV is divided into the HRSVA and HRSVB subtypes (5).

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Based on the second hypervariable region (HVR2) located in the C-terminal 94 domain of the G gene, subtypes HRSVA and HRSVB can be further classified into 95 15 genotypes and 30 genotypes, respectively (6-9). In recent years, the BA9 96 genotype with a 60-bp repeat insertion in the G protein HVR2 region has gradually 97 become the predominant genotype globally(10).            292 The authors declare that no competing interests exist.   You should focus on the genotype that you found in your samples and not conclude that the cause of outbreak are the nurses.

Conflict of interest
Response: Thank you very much for your valuable comments, we really appreciated the time that you spent in reviewing our manuscript. We agreed with you and have already revised the manuscript as you suggested.
Minor comments: Line 57, I think that a new name should not be given to the BA9 strain found. Response: Thank you very much for your comments. Sorry for the confusing name. We used the name of "SY strain" to refer the viruses identified in this study (line 58).
Line 97, You should eliminate bibliography 9 because it talks about the second hypervariable region of the G gene and citation 9 corresponds to a study of the F gene. Response: Thank you very much for your suggestion. As suggested, we deleted the bibliography 9.
Line 111-113, Because it refers to a particular strain, Shenyang (SY)? Response: Sorry for the confusing name. Shenyang (SY) strains refers to "SY strain". To avoid the confusion, we used the name of "SY strain" to refer the viruses identified in this study, in the whole manuscript.
Line 141, You must describe the methodology because it has not been previously published or is not cited. Response: Thank you very much for your comments. As suggested, we referred the reference of the real-time RT-PCR methodology in the revised manuscript (line 141).
Line 264-267, Due to the fact that it was not possible to obtain a sample from the relatives, it cannot be concluded that the outbreak was caused by the nurses. Response: Thank you very much for your comments. We agree with you. So we revised the conclusion in the manuscript: It is inferred that this outbreak of neonatal pneumonia might be spread by nursing staffs with asymptomatic infections, but could not rule out the visiting relatives who might bring the HRSV virus to the postpartum care centre.
Unfortunately, the samples were not available from the visiting relatives so that no evidence to support this speculation. Please see the modification in the line of 264-267.